COMBINATION OF CHECKPOINT INHIBITORS Checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 antibodies(Ab) have demonstrated considerable success in oncology; providing both patient benefits and commercial success. Combination immune therapeutic strategies can enhance the magnitude of the antitumor immune response over single agents. This study focuses on in vivo model to study safety and efficacy of combination of CBT- 501(anti PD-1) and CBT-502(anti PD-L1) Abs in solid tumors using a novel study design. One of the challenges in cancer drug development is the high failure rate in clinical trials and the associated high costs. This is reflective of the lack of predictive power of traditional preclinical models, where efficacy at preclinical setting fails to translate into clinical benefit. The need to reduce drug attrition is especially acute in the field of oncology, where drugs fail not only because of toxicity but also lack of efficacy. Human CD34+ hematopoietic stem cell (HSC) are engrafted into immunodeficient NOD/SCID gamma (NSG) mice. Patient derived xenograft tumors with high PD-L1 expression will be implanted subcutaneously in these mice. Now the mouse has both human PD-1 and human PD-L1 in its system and can be used to study the combination effects of the two humanized antibodies: CBT-501 and CBT-502. We propose a novel in vivo mouse study design that mimics human clinical trial: checkerboard method using two attributes. 1. Patient derived xenografts(PDX) and 2. Donor HSC. 4 PDX tumors positive for PD-L1 and 4 donor HSC will be interrogated in a n=1 checkerboard assay to yield 16 combinations mimicking human clinical trial with 16 subjects. By analyzing immune modulation in vivo in vehicle vs treated groups in this animal model can help identify useful biomarkers which can be developed as a companion diagnostic to help with commercialization. Potentially overlapping safety and tolerability when combining two agents is important to discern prior to in human trials. By characterizing differences in Mononuclear phagocyte system(MPS) interactions and response we will be able to predict systemic PK differences and toxicities in Non-human primates(NHPs) and humans. CBT is in a unique position to study this combination and develop it further in the clinic as it holds the patents for both antibodies.